Neurovirological correlation with HIV-associated neurocognitive disorders and encephalitis in a HAART-era cohort

Benjamin B. Gelman, Joshua G. Lisinicchia, Susan Morgello, Eliezer Masliah, Deborah Commins, Cristian L. Achim, Howard S Fox, Dennis L. Kolson, Igor Grant, Elyse Singer, Constantin T. Yiannoutsos, Seth Sherman, Gary Gensler, David J. Moore, Tiansheng Chen, Vicki M. Soukup

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Abstract

Objective: Replicating HIV-1 in the brain is present in HIV encephalitis (HIVE) and microglial nodule encephalitis (MGNE) and is putatively linked with HIV-associated neurocognitive disorders (HAND). A cliniconeurovirological correlation was conducted to elucidate the relationship between brain viral load and clinical phenotype. Subjects and assays: HIV gag/pol RNA and DNA copies were quantified with reverse transcriptase-polymerase chain reaction or polymerase chain reaction in 148 HAART-era brain specimens. Comparison with HAND, HIVE, and MGNE and correlation with neuropsychological (NP) test scores were done using one-way ANOVA with Tukey-Kramer and Spearman tests, respectively. Results: Brain HIV RNA was higher in subjects with HAND plus HIVE versus without HAND (delta = 2.48 log10 units, n = 27 versus 36, P , 0.001). In HAND without HIVE or MGNE, brain HIV RNA was not significantly different versus without HAND (P = 0.314). Worse NP scores correlated significantly with higher HIV RNA and interferon responses in brain specimens (P , 0.001) but not with HIV RNA levels in premortem blood plasma (n = 114) or cerebrospinal fluid (n = 104). In subjects with MGNE, brain HIV RNA was slightly higher versus without MGNE (P , 0.01) and much lower versus with HIVE (P , 0.001). Conclusions: Brain HIV RNA and to a lesser extent HIV DNA are correlated with worse NP performance in the 6 months before death. Linkage occurs primarily in patients with HIVE and MGNE, and these patients could obtain added NP improvement by further reducing brain HIV while on HAART. Patients not in those groups are less certain to obtain added NP benefit.

Original languageEnglish (US)
Pages (from-to)487-495
Number of pages9
JournalJournal of Acquired Immune Deficiency Syndromes
Volume62
Issue number5
DOIs
StatePublished - Apr 15 2013

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Highly Active Antiretroviral Therapy
Encephalitis
HIV
RNA
Brain
Neurocognitive Disorders

Keywords

  • Dementia
  • Encephalitis
  • HAND
  • HIVE
  • Interferon
  • Neurocognitive disorders

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)

Cite this

Neurovirological correlation with HIV-associated neurocognitive disorders and encephalitis in a HAART-era cohort. / Gelman, Benjamin B.; Lisinicchia, Joshua G.; Morgello, Susan; Masliah, Eliezer; Commins, Deborah; Achim, Cristian L.; Fox, Howard S; Kolson, Dennis L.; Grant, Igor; Singer, Elyse; Yiannoutsos, Constantin T.; Sherman, Seth; Gensler, Gary; Moore, David J.; Chen, Tiansheng; Soukup, Vicki M.

In: Journal of Acquired Immune Deficiency Syndromes, Vol. 62, No. 5, 15.04.2013, p. 487-495.

Research output: Contribution to journalArticle

Gelman, BB, Lisinicchia, JG, Morgello, S, Masliah, E, Commins, D, Achim, CL, Fox, HS, Kolson, DL, Grant, I, Singer, E, Yiannoutsos, CT, Sherman, S, Gensler, G, Moore, DJ, Chen, T & Soukup, VM 2013, 'Neurovirological correlation with HIV-associated neurocognitive disorders and encephalitis in a HAART-era cohort', Journal of Acquired Immune Deficiency Syndromes, vol. 62, no. 5, pp. 487-495. https://doi.org/10.1097/QAI.0b013e31827f1bdb
Gelman, Benjamin B. ; Lisinicchia, Joshua G. ; Morgello, Susan ; Masliah, Eliezer ; Commins, Deborah ; Achim, Cristian L. ; Fox, Howard S ; Kolson, Dennis L. ; Grant, Igor ; Singer, Elyse ; Yiannoutsos, Constantin T. ; Sherman, Seth ; Gensler, Gary ; Moore, David J. ; Chen, Tiansheng ; Soukup, Vicki M. / Neurovirological correlation with HIV-associated neurocognitive disorders and encephalitis in a HAART-era cohort. In: Journal of Acquired Immune Deficiency Syndromes. 2013 ; Vol. 62, No. 5. pp. 487-495.
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abstract = "Objective: Replicating HIV-1 in the brain is present in HIV encephalitis (HIVE) and microglial nodule encephalitis (MGNE) and is putatively linked with HIV-associated neurocognitive disorders (HAND). A cliniconeurovirological correlation was conducted to elucidate the relationship between brain viral load and clinical phenotype. Subjects and assays: HIV gag/pol RNA and DNA copies were quantified with reverse transcriptase-polymerase chain reaction or polymerase chain reaction in 148 HAART-era brain specimens. Comparison with HAND, HIVE, and MGNE and correlation with neuropsychological (NP) test scores were done using one-way ANOVA with Tukey-Kramer and Spearman tests, respectively. Results: Brain HIV RNA was higher in subjects with HAND plus HIVE versus without HAND (delta = 2.48 log10 units, n = 27 versus 36, P , 0.001). In HAND without HIVE or MGNE, brain HIV RNA was not significantly different versus without HAND (P = 0.314). Worse NP scores correlated significantly with higher HIV RNA and interferon responses in brain specimens (P , 0.001) but not with HIV RNA levels in premortem blood plasma (n = 114) or cerebrospinal fluid (n = 104). In subjects with MGNE, brain HIV RNA was slightly higher versus without MGNE (P , 0.01) and much lower versus with HIVE (P , 0.001). Conclusions: Brain HIV RNA and to a lesser extent HIV DNA are correlated with worse NP performance in the 6 months before death. Linkage occurs primarily in patients with HIVE and MGNE, and these patients could obtain added NP improvement by further reducing brain HIV while on HAART. Patients not in those groups are less certain to obtain added NP benefit.",
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T1 - Neurovirological correlation with HIV-associated neurocognitive disorders and encephalitis in a HAART-era cohort

AU - Gelman, Benjamin B.

AU - Lisinicchia, Joshua G.

AU - Morgello, Susan

AU - Masliah, Eliezer

AU - Commins, Deborah

AU - Achim, Cristian L.

AU - Fox, Howard S

AU - Kolson, Dennis L.

AU - Grant, Igor

AU - Singer, Elyse

AU - Yiannoutsos, Constantin T.

AU - Sherman, Seth

AU - Gensler, Gary

AU - Moore, David J.

AU - Chen, Tiansheng

AU - Soukup, Vicki M.

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N2 - Objective: Replicating HIV-1 in the brain is present in HIV encephalitis (HIVE) and microglial nodule encephalitis (MGNE) and is putatively linked with HIV-associated neurocognitive disorders (HAND). A cliniconeurovirological correlation was conducted to elucidate the relationship between brain viral load and clinical phenotype. Subjects and assays: HIV gag/pol RNA and DNA copies were quantified with reverse transcriptase-polymerase chain reaction or polymerase chain reaction in 148 HAART-era brain specimens. Comparison with HAND, HIVE, and MGNE and correlation with neuropsychological (NP) test scores were done using one-way ANOVA with Tukey-Kramer and Spearman tests, respectively. Results: Brain HIV RNA was higher in subjects with HAND plus HIVE versus without HAND (delta = 2.48 log10 units, n = 27 versus 36, P , 0.001). In HAND without HIVE or MGNE, brain HIV RNA was not significantly different versus without HAND (P = 0.314). Worse NP scores correlated significantly with higher HIV RNA and interferon responses in brain specimens (P , 0.001) but not with HIV RNA levels in premortem blood plasma (n = 114) or cerebrospinal fluid (n = 104). In subjects with MGNE, brain HIV RNA was slightly higher versus without MGNE (P , 0.01) and much lower versus with HIVE (P , 0.001). Conclusions: Brain HIV RNA and to a lesser extent HIV DNA are correlated with worse NP performance in the 6 months before death. Linkage occurs primarily in patients with HIVE and MGNE, and these patients could obtain added NP improvement by further reducing brain HIV while on HAART. Patients not in those groups are less certain to obtain added NP benefit.

AB - Objective: Replicating HIV-1 in the brain is present in HIV encephalitis (HIVE) and microglial nodule encephalitis (MGNE) and is putatively linked with HIV-associated neurocognitive disorders (HAND). A cliniconeurovirological correlation was conducted to elucidate the relationship between brain viral load and clinical phenotype. Subjects and assays: HIV gag/pol RNA and DNA copies were quantified with reverse transcriptase-polymerase chain reaction or polymerase chain reaction in 148 HAART-era brain specimens. Comparison with HAND, HIVE, and MGNE and correlation with neuropsychological (NP) test scores were done using one-way ANOVA with Tukey-Kramer and Spearman tests, respectively. Results: Brain HIV RNA was higher in subjects with HAND plus HIVE versus without HAND (delta = 2.48 log10 units, n = 27 versus 36, P , 0.001). In HAND without HIVE or MGNE, brain HIV RNA was not significantly different versus without HAND (P = 0.314). Worse NP scores correlated significantly with higher HIV RNA and interferon responses in brain specimens (P , 0.001) but not with HIV RNA levels in premortem blood plasma (n = 114) or cerebrospinal fluid (n = 104). In subjects with MGNE, brain HIV RNA was slightly higher versus without MGNE (P , 0.01) and much lower versus with HIVE (P , 0.001). Conclusions: Brain HIV RNA and to a lesser extent HIV DNA are correlated with worse NP performance in the 6 months before death. Linkage occurs primarily in patients with HIVE and MGNE, and these patients could obtain added NP improvement by further reducing brain HIV while on HAART. Patients not in those groups are less certain to obtain added NP benefit.

KW - Dementia

KW - Encephalitis

KW - HAND

KW - HIVE

KW - Interferon

KW - Neurocognitive disorders

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